Resolution of tonic concentrations of highly similar neurotransmitters using voltammetry and deep learning.

With advances in our understanding regarding the neurochemical underpinnings of neurological and psychiatric diseases, there is an increased demand for advanced computational methods for neurochemical analysis. Despite having a variety of techniques for measuring tonic extracellular concentrations of neurotransmitters, including voltammetry, enzyme-based sensors, amperometry, and in vivo microdialysis, there is currently no means to resolve concentrations of structurally similar neurotransmitters from mixtures in the in vivo environment with high spatiotemporal resolution and limited tissue damage. Since a variety of research and clinical investigations involve brain regions containing electrochemically similar monoamines, such as dopamine and norepinephrine, developing a model to resolve the respective contributions of these neurotransmitters is of vital importance. Here we have developed a deep learning network, DiscrimNet, a convolutional autoencoder capable of accurately predicting individual tonic concentrations of dopamine, norepinephrine, and serotonin from both in vitro mixtures and the in vivo environment in anesthetized rats, measured using voltammetry. The architecture of DiscrimNet is described, and its ability to accurately predict in vitro and unseen in vivo concentrations is shown to vastly outperform a variety of shallow learning algorithms previously used for neurotransmitter discrimination. DiscrimNet is shown to generalize well to data captured from electrodes unseen during model training, eliminating the need to retrain the model for each new electrode. DiscrimNet is also shown to accurately predict the expected changes in dopamine and serotonin after cocaine and oxycodone administration in anesthetized rats in vivo. DiscrimNet therefore offers an exciting new method for real-time resolution of in vivo voltammetric signals into component neurotransmitters.

Clinical evaluation of a stereotactic system for single-stage deep brain stimulation surgery under general anesthesia: technical note.

OBJECTIVE: Conventional frame-based stereotactic systems have circumferential base frames, often necessitating deep brain stimulation (DBS) surgery in two stages: intracranial electrode insertion followed by surgical re-preparation and pulse generator implantation. Some patients do not tolerate awake surgery, underscoring the need for a safe alternative for asleep DBS surgery. A frame-based stereotactic system with a skull-mounted "key" in lieu of a circumferential base frame received US FDA clearance. The authors describe the system's application for single-stage, asleep DBS surgery in 8 patients at their institution and review its workflow and technical considerations. METHODS: Eight patients underwent DBS lead insertion and IPG implantation in a single surgical preparation under general anesthesia using the system. Postoperative CT imaging confirmed lead placement. RESULTS: Eight patients underwent implantation of 15 total leads targeting the ventral intermediate nucleus (4 patients), globus pallidus internus (GPi; 3 patients), and subthalamic nucleus (STN; 1 patient). Intraoperative microelectrode recording was conducted for GPi and STN targets. Postoperative CT imaging revealed a mean ± SD radial error of 1.24 ± 0.45 mm (n = 15 leads), without surgical complications. CONCLUSIONS: The stereotactic system facilitated safe and effective asleep, single-stage DBS surgery, maintaining traditional lead accuracy standards.

Characteristics of Lambl excrescences of aortic and pulmonary valves in healthy hearts.

Lambl excrescences (LEs) were initially described in the mid-1800s during autopsies of human hearts, and their significance and biology have been debated ever since. LEs are typically found on aortic and pulmonary valve (semilunar) cusps. There is debate concerning whether LEs are a significant cause of thromboembolic events, or whether they are harmless growths. However, there have not been many reports discussing LEs, and fewer still have examined the prevalence and characteristics of LEs in healthy human hearts. Those who have examined LE prevalence have reported a very high incidence of LEs (85-90%). Herein, we examine LE prevalence and characteristics (size, location, number) in 403 healthy human hearts across all age groups. We find that the prevalence of LEs in healthy hearts is far lower than previously reported.

Techniques for Measurement of Serotonin: Implications in Neuropsychiatric Disorders and Advances in Absolute Value Recording Methods.

Serotonin (5-HT) is a monoamine neurotransmitter in the peripheral, enteric, and central nervous systems (CNS). Within the CNS, serotonin is principally involved in mood regulation and reward-seeking behaviors. It is a critical regulator in CNS pathologies such as major depressive disorder, addiction, and schizophrenia. Consequently, in vivo serotonin measurements within the CNS have emerged as one of many promising approaches to investigating the pathogenesis, progression, and treatment of these and other neuropsychiatric conditions. These techniques vary in methods, ranging from analyte sampling with microdialysis to voltammetry. Provided this diversity in approach, inherent differences between techniques are inevitable. These include biosensor size, temporal/spatial resolution, and absolute value measurement capabilities, all of which must be considered to fit the prospective researcher's needs. In this review, we summarize currently available methods for the measurement of serotonin, including novel voltammetric absolute value measurement techniques. We also detail serotonin's role in various neuropsychiatric conditions, highlighting the role of phasic and tonic serotonergic neuronal firing within each where relevant. Lastly, we briefly review the present clinical application of these techniques and discuss the potential of a closed-loop monitoring and neuromodulation system utilizing deep brain stimulation (DBS).

Race-Based Differences in ST-Segment-Elevation Myocardial Infarction Process Metrics and Mortality From 2015 Through 2021: An Analysis of 178 062 Patients From the American Heart Association Get With The Guidelines-Coronary Artery Disease Registry.

BACKGROUND: Systems of care have been developed across the United States to standardize care processes and improve outcomes in patients with ST-segment-elevation myocardial infarction (STEMI). The effect of contemporary STEMI systems of care on racial and ethnic disparities in achievement of time-to-treatment goals and mortality in STEMI is uncertain. METHODS: We analyzed 178 062 patients with STEMI (52 293 women and 125 769 men) enrolled in the American Heart Association Get With The Guidelines-Coronary Artery Disease registry between January 1, 2015, and December 31, 2021. Patients were stratified into and outcomes compared among 3 racial and ethnic groups: non-Hispanic White, Hispanic White, and Black. The primary outcomes were the proportions of patients achieving the following STEMI process metrics: prehospital ECG obtained by emergency medical services; hospital arrival to ECG obtained within 10 minutes for patients not transported by emergency medical services; arrival-to-percutaneous coronary intervention time within 90 minutes; and first medical contact-to-device time within 90 minutes. A secondary outcome was in-hospital mortality. Analyses were performed separately in women and men, and all outcomes were adjusted for age, comorbidities, acuity of presentation, insurance status, and socioeconomic status measured by social vulnerability index based on patients' county of residence. RESULTS: Compared with non-Hispanic White patients with STEMI, Hispanic White patients and Black patients had lower odds of receiving a prehospital ECG and achieving targets for door-to-ECG, door-to-device, and first medical contact-to-device times. These racial disparities in treatment goals were observed in both women and men, and persisted in most cases after multivariable adjustment. Compared with non-Hispanic White women, Hispanic White women had higher adjusted in-hospital mortality (odds ratio, 1.39 [95% CI, 1.12-1.72]), whereas Black women did not (odds ratio, 0.88 [95% CI, 0.74-1.03]). Compared with non-Hispanic White men, adjusted in-hospital mortality was similar in Hispanic White men (odds ratio, 0.99 [95% CI, 0.82-1.18]) and Black men (odds ratio, 0.96 [95% CI, 0.85-1.09]). CONCLUSIONS: Race- or ethnicity-based disparities persist in STEMI process metrics in both women and men, and mortality differences are observed in Hispanic White compared with non-Hispanic White women. Further research is essential to evolve systems of care to mitigate racial differences in STEMI outcomes.

Characteristics of aortic and pulmonary valve cusp fenestrations in healthy hearts.

Fenestrations in semilunar valves of human hearts have been incidentally described during autopsies since the 1800s, and were thought to be a degenerative process of the valve cusps. Due to the nature of autopsy, prior literature has primarily examined these fenestrations in pathologic hearts, and has implicated them in leading to valve insufficiency, regurgitation, and cusp rupture. More recent studies have predicted an increase in fenestration prevalence in the rapidly aging United States and have warned of a potential increase in fenestration-related valvular pathology. Herein, we analyze fenestration prevalence in 403 healthy human hearts and report findings that differ from these prior reports, and emphasize that fenestrations may not necessarily portend significant valvular dysfunction.

Oxycodone-induced dopaminergic and respiratory effects are modulated by deep brain stimulation.

Introduction: Opioids are the leading cause of overdose death in the United States, accounting for almost 70,000 deaths in 2020. Deep brain stimulation (DBS) is a promising new treatment for substance use disorders. Here, we hypothesized that VTA DBS would modulate both the dopaminergic and respiratory effect of oxycodone. Methods: Multiple-cyclic square wave voltammetry (M-CSWV) was used to investigate how deep brain stimulation (130 Hz, 0.2 ms, and 0.2 mA) of the rodent ventral segmental area (VTA), which contains abundant dopaminergic neurons, modulates the acute effects of oxycodone administration (2.5 mg/kg, i.v.) on nucleus accumbens core (NAcc) tonic extracellular dopamine levels and respiratory rate in urethane-anesthetized rats (1.5 g/kg, i.p.). Results: I.V. administration of oxycodone resulted in an increase in NAcc tonic dopamine levels (296.9 ± 37.0 nM) compared to baseline (150.7 ± 15.5 nM) and saline administration (152.0 ± 16.1 nM) (296.9 ± 37.0 vs. 150.7 ± 15.5 vs. 152.0 ± 16.1, respectively, p = 0.022, n = 5). This robust oxycodone-induced increase in NAcc dopamine concentration was associated with a sharp reduction in respiratory rate (111.7 ± 2.6 min-1 vs. 67.9 ± 8.3 min-1; pre- vs. post-oxycodone; p < 0.001). Continuous DBS targeted at the VTA (n = 5) reduced baseline dopamine levels, attenuated the oxycodone-induced increase in dopamine levels to (+39.0% vs. +95%), and respiratory depression (121.5 ± 6.7 min-1 vs. 105.2 ± 4.1 min-1; pre- vs. post-oxycodone; p = 0.072). Discussion: Here we demonstrated VTA DBS alleviates oxycodone-induced increases in NAcc dopamine levels and reverses respiratory suppression. These results support the possibility of using neuromodulation technology for treatment of drug addiction.

Mapping internal strain fields of fused filament fabrication metal filled polylactic acid structure using digital volume correlation.

With the advancement in Fused Filament Fabrication (FFF), its application is increasing widely across different industries such as aeronautical, biomedical, robotics, etc. The internal structure is becoming more complex and intricate with varying materials of reinforcement which are used to improve mechanical properties. Current measurement techniques like Digital Image Correlation (DIC) are non-destructive testing methods that do not provide enough information on the behaviour of internal microstructure for anisotropic FFF materials. Digital Volume Correlation (DVC) is non-destructive testing technique which provides full field internal 3D deformation and strain fields. Copper particle filled PLA samples manufactured using FFF method with 20, 40, 60 and 80 infill percentages were loaded in tension inside Micro-CT. X-rays were passed through the sample to get a volumetric dataset for different loadings. Using DVC method on the dataset, internal displacement and strain fields were generated for 20, 40, 60 and 80 infill percentage FFF sample.

Signet Ring Cell Carcinoma Presenting as a Necrotic Duodenocolic Fistulizing Mass.

A 79-year-old female was referred for endoscopic evaluation after a positive fecal occult blood test. There was a long-standing history of iron deficiency anemia, weight loss with intermittent touts of intractable vomiting, and nausea. Esophagogastroduodenoscopy revealed a secondary lumen between the duodenum and transverse colon with necrotic mucosa and a blind opening. Subsequent colonoscopy revealed similar necrotic mucosa at the transverse colon and fistula formation with communication into the duodenum. Signet ring cell carcinoma (SRCC) was evident in histologic analysis. SRCC carries a poorer prognosis than other variants of colorectal carcinoma (CRC). Proposed mechanisms of increased mucin production can lead to mucosal wall destruction and have profound manifestations, such as in our patient with duodenocolic fistula.

Micromagnetic Stimulation (µMS) Controls Dopamine Release: An in vivo Study Using WINCS Harmoni.

Objective: Research into the role of neurotransmitters in regulating normal and pathologic brain functions has made significant progress. Yet, clinical trials that aim to improve therapeutic interventions do not take advantage of the in vivo changes in the neurochemistry that occur in real time during disease progression, drug interactions or response to pharmacological, cognitive, behavioral, and neuromodulation therapies. In this work, we used the WINCS Harmoni tool to study the real time in vivo changes in dopamine release in rodent brains for the micromagnetic neuromodulation therapy. Approach: Although still in its infancy, micromagnetic stimulation (µMS) using micro-meter sized coils or microcoils (µcoils) has shown incredible promise in spatially selective, galvanic contact free and highly focal neuromodulation. These µcoils are powered by a time-varying current which generates a magnetic field. As per Faraday's Laws of Electromagnetic Induction, this magnetic field induces an electric field in a conducting medium (here, the brain tissues). We used a solenoidal-shaped µcoil to stimulate the medial forebrain bundle (MFB) of the rodent brain in vivo. The evoked in vivo dopamine releases in the striatum were tracked in real time by carbon fiber microelectrodes (CFM) using fast scan cyclic voltammetry (FSCV). Results: Our experiments report that µcoils can successfully activate the MFB in rodent brains, triggering dopamine release in vivo. We further show that the successful release of dopamine upon micromagnetic stimulation is dependent on the orientation of the µcoil. Furthermore, varied intensities of µMS can control the concentration of dopamine releases in the striatum. Significance: This work helps us better understand the brain and its conditions arising from a new therapeutic intervention, like µMS, at the level of neurotransmitter release. Despite its early stage, this study potentially paves the path for µMS to enter the clinical world as a precisely controlled and optimized neuromodulation therapy.

Deep brain stimulation alleviates tics in Tourette syndrome via striatal dopamine transmission.

Tourette syndrome is a childhood-onset neuropsychiatric disorder characterized by intrusive motor and vocal tics that can lead to self-injury and deleterious mental health complications. While dysfunction in striatal dopamine neurotransmission has been proposed to underlie tic behaviour, evidence is scarce and inconclusive. Deep brain stimulation (DBS) of the thalamic centromedian parafascicular complex (CMPf), an approved surgical interventive treatment for medical refractory Tourette syndrome, may reduce tics by affecting striatal dopamine release. Here, we use electrophysiology, electrochemistry, optogenetics, pharmacological treatments and behavioural measurements to mechanistically examine how thalamic DBS modulates synaptic and tonic dopamine activity in the dorsomedial striatum. Previous studies demonstrated focal disruption of GABAergic transmission in the dorsolateral striatum of rats led to repetitive motor tics recapitulating the major symptom of Tourette syndrome. We employed this model under light anaesthesia and found CMPf DBS evoked synaptic dopamine release and elevated tonic dopamine levels via striatal cholinergic interneurons while concomitantly reducing motor tic behaviour. The improvement in tic behaviour was found to be mediated by D2 receptor activation as blocking this receptor prevented the therapeutic response. Our results demonstrate that release of striatal dopamine mediates the therapeutic effects of CMPf DBS and points to striatal dopamine dysfunction as a driver for motor tics in the pathoneurophysiology of Tourette syndrome.

High frequency deep brain stimulation can mitigate the acute effects of cocaine administration on tonic dopamine levels in the rat nucleus accumbens.

Cocaine's addictive properties stem from its capacity to increase tonic extracellular dopamine levels in the nucleus accumbens (NAc). The ventral tegmental area (VTA) is a principal source of NAc dopamine. To investigate how high frequency stimulation (HFS) of the rodent VTA or nucleus accumbens core (NAcc) modulates the acute effects of cocaine administration on NAcc tonic dopamine levels multiple-cyclic square wave voltammetry (M-CSWV) was used. VTA HFS alone decreased NAcc tonic dopamine levels by 42%. NAcc HFS alone resulted in an initial decrease in tonic dopamine levels followed by a return to baseline. VTA or NAcc HFS following cocaine administration prevented the cocaine-induced increase in NAcc tonic dopamine. The present results suggest a possible underlying mechanism of NAc deep brain stimulation (DBS) in the treatment of substance use disorders (SUDs) and the possibility of treating SUD by abolishing dopamine release elicited by cocaine and other drugs of abuse by DBS in VTA, although further studies with chronic addiction models are required to confirm that. Furthermore, we demonstrated the use of M-CSWV can reliably measure tonic dopamine levels in vivo with both drug administration and DBS with minimal artifacts.

Left Ventricular Strain from Myocardial Perfusion PET Imaging: Method Development and Comparison to 2-Dimensional Echocardiography.

This study aimed to develop a measure of longitudinal, radial, and circumferential myocardial strain at rest and regadenoson during pharmacologic stress using 82Rb PET electrocardiography-gated myocardial perfusion imaging (MPI). Methods: We retrospectively identified 80 patients who underwent rest and regadenoson-stress CT attenuation-corrected 82Rb PET and had a standard resting transthoracic echocardiogram (TTE) with global longitudinal strain (GLS) analysis within 3 mo. A method was developed to compute longitudinal, radial, and circumferential strain from PET MPI at stress and rest. PET MPI-derived strain and left ventricular function were compared with resting TTE measures as the clinical reference standard. Interobserver agreement of PET MPI strain and left ventricular ejection fraction processing was reported. Results: Longitudinal strain assessed with resting TTE GLS showed good correlation with PET MPI at stress (r = 0.68, P < 0.001) and rest (r = 0.58, P < 0.001). Resting TTE GLS also correlated with PET MPI radial strain at stress (r = -0.70, P < 0.001) and rest (r = -0.59, P < 0.001) and circumferential strain at stress (r = 0.67, P < 0.001) and rest (r = 0.69, P < 0.001). The left ventricular ejection fraction showed good correlation between resting TTE and PET MPI at stress (r = 0.83, P < 0.001) and rest (r = 0.80, P < 0.001). Bland-Altman analysis indicated positive bias of TTE GLS compared with PET MPI longitudinal strain at stress (mean difference = 5.1%, 95% CI = [-2.5, 12.7]) and rest (mean difference = 4.2%, 95% CI = [-4.3, 12.8]). Reproducibility of PET MPI longitudinal strain showed good agreement at stress (concordance correlation coefficient = 0.73, P < 0.001) and rest (concordance correlation coefficient = 0.74, P < 0.001), with Bland-Altman analysis showing a small bias in the longitudinal direction at stress (mean difference = -0.2%) and rest (mean difference = -1.0%). Conclusion: Strain measured with PET MPI using an automated technique correlated well with resting GLS strain obtained by TTE, and the measure is reproducible. Strain from PET MPI should be investigated further to establish reference ranges and assess its value in routine clinical practice.

Comparison of the impact of skull density ratio with alternative skull metrics on magnetic resonance-guided focused ultrasound thalamotomy for tremor.

OBJECTIVE: One of the key metrics that is used to predict the likelihood of success of MR-guided focused ultrasound (MRgFUS) thalamotomy is the overall calvarial skull density ratio (SDR). However, this measure does not fully predict the sonication parameters that would be required or the technical success rates. The authors aimed to assess other skull characteristics that may also contribute to technical success. METHODS: The authors retrospectively studied consecutive patients with essential tremor who were treated by MRgFUS at their center between 2017 and 2021. They evaluated the correlation between the different treatment parameters, particularly maximum power and energy delivered, with a range of patients' skull metrics and demographics. Machine learning algorithms were applied to investigate whether sonication parameters could be predicted from skull density metrics alone and whether including combined local transducer SDRs with overall calvarial SDR would increase model accuracy. RESULTS: A total of 62 patients were included in the study. The mean age was 77.1 (SD 9.2) years, and 78% of treatments (49/63) were performed in males. The mean SDR was 0.51 (SD 0.10). Among the evaluated metrics, SDR had the highest correlation with the maximum power used in treatment (ρ = -0.626, p < 0.001; proportion of local SDR values ≤ 0.8 group also had ρ = +0.626, p < 0.001) and maximum energy delivered (ρ = -0.680, p < 0.001). Machine learning algorithms achieved a moderate ability to predict maximum power and energy required from the local and overall SDRs (accuracy of approximately 80% for maximum power and approximately 55% for maximum energy), and high ability to predict average maximum temperature reached from the local and overall SDRs (approximately 95% accuracy). CONCLUSIONS: The authors compared a number of skull metrics against SDR and showed that SDR was one of the best indicators of treatment parameters when used alone. In addition, a number of other machine learning algorithms are proposed that may be explored to improve its accuracy when additional data are obtained. Additional metrics related to eventual sonication parameters should also be identified and explored.

Treatment Time and In-Hospital Mortality Among Patients With ST-Segment Elevation Myocardial Infarction, 2018-2021.

Importance: Recognizing the association between timely treatment and less myocardial injury for patients with ST-segment elevation myocardial infarction (STEMI), US national guidelines recommend specific treatment-time goals. Objective: To describe these process measures and outcomes for a recent cohort of patients. Design, Setting, and Participants: Cross-sectional study of a diagnosis-based registry between the second quarter of 2018 and the third quarter of 2021 for 114 871 patients with STEMI treated at 648 hospitals in the Get With The Guidelines-Coronary Artery Disease registry. Exposures: STEMI or STEMI equivalent. Main Outcomes and Measures: Treatment times, in-hospital mortality, and adherence to system goals (75% treated ≤90 minutes of first medical contact if the first hospital is percutaneous coronary intervention [PCI]-capable and ≤120 minutes if patients require transfer to a PCI-capable hospital). Results: In the study population, median age was 63 (IQR, 54-72) years, 71% were men, and 29% were women. Median time from symptom onset to PCI was 148 minutes (IQR, 111-226) for patients presenting to PCI-capable hospitals by emergency medical service, 195 minutes (IQR, 127-349) for patients walking in, and 240 minutes (IQR, 166-402) for patients transferred from another hospital. Adjusted in-hospital mortality was lower for those treated within target times vs beyond time goals for patients transported via emergency medical services (first medical contact to laboratory activation ≤20 minutes [in-hospital mortality, 3.6 vs 9.2] adjusted OR, 0.54 [95% CI, 0.48-0.60], and first medical contact to device ≤90 minutes [in-hospital mortality, 3.3 vs 12.1] adjusted OR, 0.40 [95% CI, 0.36-0.44]), walk-in patients (hospital arrival to device ≤90 minutes [in-hospital mortality, 1.8 vs 4.7] adjusted OR, 0.47 [95% CI, 0.40-0.55]), and transferred patients (door-in to door-out time <30 minutes [in-hospital mortality, 2.9 vs 6.4] adjusted OR, 0.51 [95% CI, 0.32-0.78], and first hospital arrival to device ≤120 minutes [in-hospital mortality, 4.3 vs 14.2] adjusted OR, 0.44 [95% CI, 0.26-0.71]). Regardless of mode of presentation, system goals were not met in most quarters, with the most delayed system performance among patients requiring interhospital transfer (17% treated ≤120 minutes). Conclusions and Relevance: This study of patients with STEMI included in a US national registry provides information on changes in process and outcomes between 2018 and 2021.

Emergency Interhospital Transfer of Patients With ST-Segment-Elevation Myocardial Infarction: Call 9-1-1-The American Heart Association Mission: Lifeline Program.

The American Heart Association Mission: Lifeline program objectives are to improve the quality of care and outcomes for patients with ST-segment-elevation myocardial infarction. Every minute of delay in treatment adversely affects 1-year mortality. Transfer of patients safely and timely to hospitals with primary percutaneous coronary intervention capability is needed to improve outcomes. But treatment times continue to show delays, especially during interhospital transfers. A simple 3-step process of an interhospital "Call 9-1-1" protocol may expedite this process. This STAT TRANSFER process uses a systems approach that considers diverse ways in which patients access care, how EMS responds and determines destinations, how referring hospital transfers are performed, urban and rural differences, and how receiving hospitals prepare for an incoming patient with ST-segment-elevation myocardial infarction. This initiative suggests a strategy to reduce variability in interhospital transfer times using a STAT TRANSFER and a Call 9-1-1 process in a system of care that involves all stakeholders.

Software for near-real-time voltammetric tracking of tonic neurotransmitter levels in vivo.

Tonic extracellular neurotransmitter concentrations are important modulators of central network homeostasis. Disruptions in these tonic levels are thought to play a role in neurologic and psychiatric disease. Therefore, ways to improve their quantification are actively being investigated. Previously published voltammetric software packages have implemented FSCV, which is not capable of measuring tonic concentrations of neurotransmitters in vivo. In this paper, custom software was developed for near-real-time tracking (scans every 10 s) of neurotransmitters' tonic concentrations with high sensitivity and spatiotemporal resolution both in vitro and in vivo using cyclic voltammetry combined with dynamic background subtraction (M-CSWV and FSCAV). This software was designed with flexibility, speed, and user-friendliness in mind. This software enables near-real-time measurement by reducing data analysis time through an optimized modeling algorithm, and efficient memory handling makes long-term measurement possible. The software permits customization of the cyclic voltammetric waveform shape, enabling experiments to detect a specific analyte of interest. Finally, flexibility considerations allow the user to alter the fitting parameters, filtering characteristics, and size and shape of the analyte kernel, based on data obtained live during the experiment to obtain accurate measurements as experimental conditions change. Herein, the design and advantages of this near-real-time voltammetric software are described, and its use is demonstrated in in vivo experiments.

Development and Evaluation of a Core Genome Multilocus Sequencing Typing (cgMLST) Scheme for Serratia marcescens Molecular Surveillance and Outbreak Investigations.

Serratia marcescens can cause a range of severe infections and contributes to nosocomial outbreaks. Although whole-genome sequencing (WGS)-based typing is the standard method for molecular surveillance and outbreak investigation, there is no standardized analytic scheme for S. marcescens core genome multilocus sequence typing (cgMLST). Here, the development and evaluation of a S. marcescens cgMLST scheme is reported with the goal of enabling a standardized methodology and typing nomenclature. Four hundred ninety-one high-quality S. marcescens WGS data sets were extracted from public databases and-using the genomic sequence of NCBI reference strain S. marcescens Db11 (NZ_HG326223.1) as a starting point-all Db11 genes present in ≥97% data sets used to create a cgMLST scheme. The novel scheme was evaluated using WGS data from 24 outbreak investigations (n = 175 isolates) distributed over three continents. Analysis of Db11 genes within the 491 data sets identified 2,692 target genes present in ≥97% of genomes (mean, 99.1%; median, 99.9%). These genes formed the novel cgMLST scheme, covering 47.8% of nucleotides in the Db11 genome. Analyzing 175 isolates from 24 outbreaks using the novel scheme gave comparable results to previous typing efforts for both general groupings and allelic distances within clusters. In summary, a novel cgMLST scheme for S. marcescens was developed and evaluated. The scheme and its associated nomenclature will improve standardization of typing efforts for molecular surveillance and outbreak investigation, allowing better understanding of S. marcescens genomic epidemiology and facilitating interlaboratory comparisons.

Use of primary bariatric surgery among patients with obesity and diabetes. Insights from the Diabetes Collaborative Registry.

Despite its cardiometabolic benefits, bariatric surgery has historically been underused in patients with obesity and diabetes, but contemporary data are lacking. Among 1,520,182 patients evaluated from 2013 to 2019 within a multicenter, longitudinal, US registry of outpatients with diabetes, we found that 462,033 (30%) met eligibility for bariatric surgery. After a median follow-up of 854 days, 6310/384,859 patients (1.6%) underwent primary bariatric surgery, with a slight increase over time (0.38% per year [2013] to 0.68% per year [2018]). Patients who underwent bariatric surgery were more likely to be female (63% vs. 56%), white (87% vs. 82%), have higher body mass indices (42.1 ± 6.9 vs. 40.6 ± 5.9 kg/m2), and depression (23% vs. 14%; p < 0.001 for all). Over a median (IQR) follow-up after surgery of 722 days (364-993), patients who underwent bariatric surgery had lost an average of 11.8 ± 18.5 kg (23% of excess body weight), 10.2% were on fewer glucose-lowering medications, and 8.4% were on fewer antihypertensives. Despite bariatric surgery being safer and more accessible over the past two decades, less than one in fifty eligible patients with diabetes receive this therapy.

County-Level Social Vulnerability is Associated With In-Hospital Death and Major Adverse Cardiovascular Events in Patients Hospitalized With COVID-19: An Analysis of the American Heart Association COVID-19 Cardiovascular Disease Registry.

BACKGROUND: The COVID-19 pandemic has disproportionately affected low-income and racial/ethnic minority populations in the United States. However, it is unknown whether hospitalized patients with COVID-19 from socially vulnerable communities experience higher rates of death and/or major adverse cardiovascular events (MACEs). Thus, we evaluated the association between county-level social vulnerability and in-hospital mortality and MACE in a national cohort of hospitalized COVID-19 patients. METHODS: Our study population included patients with COVID-19 in the American Heart Association COVID-19 Cardiovascular Disease Registry across 107 US hospitals between January 14, 2020 to November 30, 2020. The Social Vulnerability Index (SVI), a composite measure of community vulnerability developed by Centers for Disease Control and Prevention, was used to classify the county-level social vulnerability of patients' place of residence. We fit a hierarchical logistic regression model with hospital-level random intercepts to evaluate the association of SVI with in-hospital mortality and MACE. RESULTS: Among 16 939 hospitalized COVID-19 patients in the registry, 5065 (29.9%) resided in the most vulnerable communities (highest national quartile of SVI). Compared with those in the lowest quartile of SVI, patients in the highest quartile were younger (age 60.2 versus 62.3 years) and more likely to be Black adults (36.7% versus 12.2%) and Medicaid-insured (31.1% versus 23.0%). After adjustment for demographics (age, sex, race/ethnicity) and insurance status, the highest quartile of SVI (compared with the lowest) was associated with higher likelihood of in-hospital mortality (OR, 1.25 [1.03-1.53]; P=0.03) and MACE (OR, 1.26 [95% CI, 1.05-1.50]; P=0.01). These findings were not attenuated after accounting for clinical comorbidities and acuity of illness on admission. CONCLUSIONS: Patients hospitalized with COVID-19 residing in more socially vulnerable communities experienced higher rates of in-hospital mortality and MACE, independent of race, ethnicity, and several clinical factors. Clinical and health system strategies are needed to improve health outcomes for socially vulnerable patients.